Re-Purposed Drug Could Treat Alzheimer's Disease
Rolofylline could prevent clumps of Tau protein associated with certain cognitive disorders.
The results of a new study suggest that Rolofylline could potentially be used to treat learning and memory problems that are characteristic of conditions associated with aggregating Tau proteins, such as Alzheimer’s disease.
Normally functioning Tau stabilizes the routes that are needed for transporting cellular components within axons in the brain. In conditions where Tau malfunctions, as seen in Alzheimer’s disease, the protein becomes toxic and stops transporting materials, which leads to cell death.
This effects neuronal function and leads to impaired cognition. There is currently no treatment for Tau-associated conditions, since the mechanisms are largely unknown.
Researchers in the current study, published by the Proceedings of the National Academy of Sciences, made discoveries regarding the pathological processes involving Tau.
Small clumps of Tau collect in the axons and cause neurons to rest, causing diminished neuronal activity. The researchers found that the drug Rolofylline is able to increase neuronal activity, regardless of the production of Tau.
The drug was also found to magnify signal transmission and reception to increase nerve cell communication. It was also seen to relieve learning and memory deficits in mice models, according to the study.
Rolofylline was created to treat patients with kidney dysfunction, as well as heart failure. It works by binding to adenosine A1 receptors, and blocks signal pathways that would decrease neuronal activity.
However, the development of the drug was terminated when it did not prove to be more effective than placebo in these patients. Re-purposing the drug may provide new treatment options for patients with Tau-associated diseases.
“Our results suggest that Rolofylline could potentially be useful to treat neuronal dysfunctions that occur in tauopathies. This makes the drug a hot candidate for further studies,” said first author Frank Dennissen, PhD. “As an analogy, the Tau aggregates resemble a concrete wall in the middle of the room which blocks a WiFi signal. Rolofylline seems to work as a WiFi booster that can re-establish the connection despite of the obstruction.”